Abstract
Background
Erdheim Chester disease (non-Langerhan’s cell histocytosis) is a poorly recognised rare multisystem disorder. Alfa interferon (αINF) is recommended as initial therapy. BRAFV600E and MAP2K1 mutations have been identified in this condition, for which targeted biologic therapy is now available. We present a clinically challenging case of ECD, including both small and large vessel vasculitis, intolerant of αINF, who has now responded well to MAP2KI inhibition.
Methods
A 49-year-old gentleman was referred to the rheumatology clinic in 2013 with a multisystem inflammatory condition, initially characterised by weight loss, systemic upset, cranial diabetes insipidus and hypogonadism, testicular masses, lymphadenopathy and knee arthritis. Initial PET scan demonstrated uptake in these areas, together with the typical long bone pattern of uptake of ECD with complete enhancement of the pituitary on MRI. Non-Langerhan’s cell histocytosis was confirmed histologically from synovial biopsy, with presence of the MAP2K1 mutation. He was initially treated with αINF, which he was unable to tolerate, and he was then maintained on a combination of subcutaneous methotrexate and prednisolone. In 2017, he developed transient weakness and dysarthria, and episcleritis with DSA-MRI consistent with small vessel cerebral vasculitis. This was treated with cyclophosphamide. 6 months later, he experienced amaurosis fugax. He was found to have critically stenotic carotid arteries, despite these being normal when imaged 6 months previously. Carotid artery biopsy confirmed non-giant cell vasculitic changes, and PET confirmed large vessel uptake from carotids to aortic arch.
Results
Funding for targeted biologic therapy was turned down by NHSE. Trametib, a MEK1 inhibitor was obtained on compassionate grounds. Following commencement of this, PET uptake in all areas, including the vasculature normalised, with symptomatic resolution and CRP falling from 148 to 4. At the 6-month point, he remains in remission symptomatically, radiographically and in laboratory markers.
Conclusion
ECD is a rare multi-system disorder characterised by tissue infiltration of foamy histiocytes. There are approximately 550 cases described in the literature. It is classified as an inflammatory myeloid neoplasm, with variable phenotype and prognosis. Median survival is 162 months. CNS involvement and lack of response to α-INF are both independent predictors of a poor prognosis. Two genetic mutations have been identified in these patients: BRAFV600E in over 60% and MAP2K1 in 20%. Both mutations now have targeted biologic inhibition. ECD may present in the rheumatology clinic due to its inflammatory and multisystem involvement. We hope to promote recognition of this condition through this case. Although targeted therapies exist, better avenues of funding need to be available for patients with rare conditions to access them.
Disclosures
H. Alkoky None. T. Munir None. F. Borg None.
Erdheim-Chester Disease with No Skeletal Bone Involvement and Massive Weight Loss
